prevalence of occult hepatitis b virus infection（obi） in subjects with chronic hepatitis b（chb） family history

Conditions: Chronic Hepatitis b

Summary: mother to child transmission is the main route of hepatitis b virus (hbv) transmission in china, attributing to over 50% hbv infection. familial aggregation in hbv infection is well recognized with underlying stipulations like mother-to-child transmission（mtct）, susceptible genes, close contact and other factors. not surprisingly, a large proportion of hepatitis b virus infected population in china have a family history of hepatitis b virus infection. in clinical practice those family members usually undergo merely hepatitis b virus serology tests without hbv dna test, which ruled out false hbsag (-) or occult hbv infection (obi) from screening and linkage to care (sltc). unfortunately, the missed-out obi in chb family members was of a greater prevalence compared to those from general population (8.0% vs. 2.6%) . moreover, obi has been well recognized as strong risk factor in hepatocellular carcinoma （hcc） development with significant hbv dna integration into host genome . in light of the latest 2019 china chb guidelines, treatment criteria covered subjects with family history of chb related cirrhosis or hepatocellular carcinoma(hcc). therefore, subjects of hbsag (+) with normal alanine aminotransferase（alt） or obi are eligible for further consideration of hbv anti-viral treatment. this study proposed will explore the prevalence of obi in subjects with family history of hbv related cirrhosis or hcc. the screened hbsag (+) with normal alanine aminotransferase(alt) and obi subjects would be linked to anti-viral therapies.

serum samples were tested for liver enzymes and liver synthesis function including alt, aspartate aminotransferase（ast）, and albumin, etc. using a hitachi 7600 automatic analyzer and reagent system (hitachi, tokyo, japan). hbsag quantification was performed using automated electrochemiluminescence immunoassay (eclia) manufactured by roche. hbsab, hbeag, hbeab and hbcab were measured semi-quantitatively using chemiluminescence immunoassay (clia) manufactured by abbott diagnostics (usa). serum hbv dna levels were measured using the cobas taqman hbv monitor test, with a lower limit of detection of 20 iu/ml (100 copies/ml). the false negative result excluding obi due to real time pcr (lower limit of 20 iu/ml) technically may exist. the study group plan to carry out nested pcr (specifically target the hbv pre-s, s, pre-c/core, and x open reading frames) on subjects with hbsag (-) hbv dna (-) and hbcab(+) to double check the potential false negative result in hbv dna from real time pcr. quantitation of intrahepatic hbv cccdna by quantitative real-time pcr (qpcr).

Eligibility criteria:
inclusion criteria: * first- and second-degree relatives of chb patients in west china； * subjects with family history of chb related cirrhosis or hcc; * subjects with ability to understand and sign a written informed consent form. exclusion criteria: * positive antibody against hepatitis c virus(hcv),hepatitis d virus(hdv), or human immunodeficiency virus(hiv) (anti-hcv, anti-hdv, or anti-hiv) * evidence of other autoimmune or metabolic liver diseases (except non-alcoholic fatty liver disease). * moribund state including advanced/pre-terminal liver cancer or other non-hepatic cancers * non-hepatic cancer undergoing chemotherapy within last 6 months